The performance of the Sudoscan technology for diagnosing diabetic polyneuropathy (DPN) was evaluated against the quantitative sudomotor axon reflex test (QSART). Furthermore, the association of ...Sudoscan with two clinical neuropathy scoring systems was evaluated.
Forty-seven patients with type 2 diabetes (20 without DPN, 27 with DPN) and 16 matched controls were examined for neuropathic symptoms and for the extent of sensory deficits. Sweat latency and volume by QSART and the skin electrochemical conductance (ESC) by Sudoscan were measured.
The feet and hand ESC was significantly lower in patients with DPN as compared to controls. Patients with DPN had also lower hand ESC than patients without DPN. Sensitivity and specificity of feet and hand ESC for detecting DPN were 70/85% and 53/50% respectively. QSART could not differentiate between the three groups. ESC was inversely related to neuropathic symptoms and sensory impairment. ESC was significantly correlated with sensory impairment and pain.
Sudoscan shows a good performance in detecting subjects with DPN and it correlates well with clinical signs and symptoms of neuropathy.
This study provides evidence that Sudoscan has high potential to be used as screening tool for DPN and possibly also for small fiber neuropathy in diabetic patients.
- The sudomotor function test Sudoscan shows a good performance to detect diabetes peripheral neuropathy.- Sudoscan measures significantly correlate with clinical signs and symptoms of neuropathy.- The Sudoscan technology may help to secure clinical diagnosis of small fiber neuropathy.
It is well-known that initiation of fingolimod induces a transient decrease of heart rate. However, the underlying cardiac autonomic regulation is poorly understood. We aimed to investigate the ...changes of autonomic activity caused by the first dose of fingolimod using a long-term multiple trigonometric spectral analysis for the first time. In addition, we sought to use the continuous Holter ECG recording to find predictors for fingolimod induced bradycardia.
Seventy-eight patients with relapsing-remitting multiple sclerosis (RRMS) were included. As a part of the START study (NCT01585298), continuous electrocardiogram was recorded before fingolimod initiation, and until no <6 h post medication. Time domain and frequency domain heart rate variability (HRV) parameters were computed hourly to assess cardiac autonomic regulation. A long-term multiple trigonometric regressive spectral (MTRS) analysis was applied on successive 1-h-length electrocardiogram recordings. Decision tree analysis was used to find predictors for bradycardia following fingolimod initiation.
Most of the HRV parameters representing parasympathetic activities began to increase since the second hour after fingolimod administration. These changes of autonomic regulations were in accordance with the decline of heart rate. Baseline heart rate was highly correlated with nadir heart rate, and was the only significant predicting factor for fingolimod induced bradycardia among various demographic, clinical and cardiovascular variables in the decision tree analysis.
The first dose application of fingolimod enhances the cardiac parasympathetic activity during the first 6 h post medication, which might be the underlying autonomic mechanism of reduced heart rate. Baseline heart rate is a powerful predictor for bradycardia caused by fingolimod.
We aimed to explore the effects of bilateral subthalamic nucleus stimulation and levodopa on cardiovascular autonomic function in Parkinson's disease. Twenty-six Parkinson's disease patients with ...bilateral subthalamic nucleus stimulation in a stable state were tested under stimulation off and dopaminergic medication off (OFF-OFF), stimulation on and dopaminergic medication off (ON-OFF), and stimulation on and medication (levodopa) on (ON-ON) conditions by recording continuously blood pressure, ECG, and respiration at rest, during metronomic deep breathing, and head-up tilt test. Thirteen patients were diagnosed as orthostatic hypotension by head-up tilt test. Baroreflex sensitivity and spectral analyses were performed by trigonometric regressive spectral analysis. Subthalamic nucleus stimulation and levodopa had multiple influences. (1) Systolic blood pressure during tilt-up was reduced by subthalamic nucleus stimulation, and then further by levodopa. (2) Subthalamic nucleus stimulation and levodopa had different effects on sympathetic and parasympathetic regulations in Parkinson's disease. (3) Levodopa decreased baroreflex sensitivity and RR interval only in the orthostatic hypotension group, and had opposite effects on the non-orthostatic hypotension group. These findings indicate that subthalamic nucleus stimulation and levodopa have different effects on cardiovascular autonomic function in Parkinson's disease, which are modulated by the presence of orthostatic hypotension as well.
Differences in spontaneous and drug-induced baroreflex sensitivity (BRS) have been attributed to its different operating ranges. The current study attempted to compare BRS estimates during ...cardiovascular steady-state and pharmacologically stimulation using an innovative algorithm for dynamic determination of baroreflex gain.
Forty-five volunteers underwent the modified Oxford maneuver in supine and 60° tilted position with blood pressure and heart rate being continuously recorded. Drug-induced BRS-estimates were calculated from data obtained by bolus injections of nitroprusside and phenylephrine. Spontaneous indices were derived from data obtained during rest (stationary) and under pharmacological stimulation (non-stationary) using the algorithm of trigonometric regressive spectral analysis (TRS). Spontaneous and drug-induced BRS values were significantly correlated and display directionally similar changes under different situations. Using the Bland-Altman method, systematic differences between spontaneous and drug-induced estimates were found and revealed that the discrepancy can be as large as the gain itself. Fixed bias was not evident with ordinary least products regression. The correlation and agreement between the estimates increased significantly when BRS was calculated by TRS in non-stationary mode during the drug injection period. TRS-BRS significantly increased during phenylephrine and decreased under nitroprusside.
The TRS analysis provides a reliable, non-invasive assessment of human BRS not only under static steady state conditions, but also during pharmacological perturbation of the cardiovascular system.
Retinal neovascularization characterizes proliferative diabetic retinopathy (PDR). Pigment epithelium-derived factor (PEDF) has been shown to be a major antiangiogenic growth factor in the mammalian ...eye. PEDF expression is suppressed by hypoxia, and changes in PEDF have been correlated to the development of retinal neovascularization in animal models of hypoxic eye disease. However, whether this concept of a reduced angiogenesis inhibitor holds true in humans is as yet unclear. In this study, we analyzed the in vivo regulation of PEDF in patients with and without hypoxic eye disease. We used immunoblots to measure PEDF in ocular fluids obtained from 64 nondiabetic and diabetic patients. In addition, immunohistochemistry of PEDF was carried out in specimens of normal human retinas and retinas with various degrees of diabetic retinopathy. The PEDF concentrations in patients with PDR (P < 0.001) or extensive nondiabetic retinal neovascularization caused by retinal-vein occlusion (P < 0.001) were lower than in control patients. Levels of PEDF were replenished in PDR patients with previous retinal scatter photocoagulation compared with PDR patients without previous photocoagulation (P = 0.01). Immunohistochemistry revealed an interstitial staining pattern as expected for a secreted protein, with an intense staining in retinas of patients without proliferative eye disease. However, in patients with PDR, little or no staining was detectable. Our data strongly support the concept that retinal angiogenesis is induced by loss of the major angiogenesis inhibitor in the eye, PEDF, in combination with an increased expression of angiogenic growth factors such as vascular endothelial growth factor. Our findings suggest that substitution of angiogenesis inhibitors may be an effective approach in the treatment of PDR.
The assessment of baroreflex sensitivity (BRS) has emerged as prognostic tool in cardiology. Although available computer-assisted methods, measuring spontaneous fluctuations of heart rate and blood ...pressure in the time and frequency domain are easily applicable, they do not allow for quantification of BRS during cardiovascular adaption processes. This, however, seems an essential criterion for clinical application. We evaluated a novel algorithm based on trigonometric regression regarding its ability to map dynamic changes in BRS and autonomic tone during cardiovascular provocation in relation to gender and age.
We continuously recorded systemic arterial pressure, electrocardiogram and respiration in 23 young subjects (25+/-2 years) and 22 middle-aged subjects (56+/-4 years) during cardiovascular autonomic testing (metronomic breathing, Valsalva manoeuvre, head-up tilt). Baroreflex- and spectral analysis was performed using the algorithm of trigonometric regressive spectral analysis. There was an age-related decline in spontaneous BRS and high frequency oscillations of RR intervals. Changes in autonomic tone evoked by cardiovascular provocation were observed as shifts in the ratio of low to high frequency oscillations of RR intervals and blood pressure. Respiration at 0.1 Hz elicited an increase in BRS while head-up tilt and Valsalva manoeuvre resulted in a downregulation of BRS. The extent of autonomic adaption was in general more pronounced in young individuals and declined stronger with age in women than in men.
The trigonometric regressive spectral analysis reliably maps age- and gender-related differences in baroreflex- and autonomic function and is able to describe adaption processes of baroreceptor circuit during cardiovascular stimulation. Hence, this novel algorithm may be a useful screening tool to detect abnormalities in cardiovascular adaption processes even when resting values appear to be normal.
Background: Carotid endarterectomy (CEA) is the first-line treatment in severe carotid stenosis to prevent stroke. Because of methodological limitations, the acute impact of CEA on baroreflex ...function and cerebral autoregulation is not well defined and was therefore investigated by applying a novel algorithm. Methods and Results: Systemic arterial blood pressure, ECG and respiration during metronomic breathing and Valsalva maneuver were continuously recorded in 18 patients with carotid stenosis before and after CEA, and in 10 healthy controls. Baroreflex sensitivity, frequency spectra of RR intervals and indices for cerebral autoregulation were evaluated by trigonometric regressive spectral analysis. Compared with the controls, patients had impaired baroreflex sensitivity. Baroreflex sensitivity and frequency spectra were not changed by CEA. Cerebral autoregulation of patients with carotid stenosis as calculated by phase shift was reduced compared with controls but it improved significantly after CEA. Improvement of cerebral autoregulation was independent of changes in cerebral blood flow velocity. Conclusions: Baroreflex sensitivity and cerebral autoregulation are impaired in patients with carotid stenosis, conferring a high stroke risk. CEA improves cerebral autoregulation, but does not affect baroreflex sensitivity. For further risk reduction, interventional approaches targeting baroreflex function need to be considered. (Circ J 2010; 74: 2139-2145)
Abstract Objective To assess the risk factor pattern of the metabolic syndrome and its association with insulin resistance and hyperuricaemia in a sub-Saharan African population with different levels ...of urbanisation. Methods Four hundred forty-eight black South African volunteers, men and women aged 15 years and older were investigated in a cross-sectional, comparative, population-based survey. Subjects were stratified into three groups representing different levels of urbanisation in rural and urban areas. The metabolic syndrome was defined according to IDF criteria. Factor analysis was used to examine the risk factor pattern of the metabolic syndrome. Results The prevalence of the metabolic syndrome was low and did not differ across the three groups. Factor analysis showed slight differences in the metabolic syndrome pattern between the groups. Hyperuricaemia–hypertriglyceridaemia was identified as distinct component in the rural and semiurban group whereas hyperinsulinaemia was loaded together with other risk factors. In the entire study population, five factors could be identified in the following sequence: obesity, hypertension, hyperuricaemia–hypertriglyceridaemia, hyperglycaemia and hyperinsulinaemia. Subjects with hyperuricaemia but not with insulin resistance exhibited an increased risk to develop the metabolic syndrome. Conclusions Hyperuricaemia was revealed as additional component of the metabolic syndrome in sub-Saharan Africans and should be given more attention in prevention settings.
Background Research demonstrated a significant relationship between elevated nocturnal blood pressure and sympathetic hyperactivity. The study aimed to investigate possible associations between ...norepinephrine metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), nocturnal BP and carotid intima-media thickness (CIMT) in urban African and Caucasian men. Methods The study included 82 African and 100 Caucasian male teachers, aged 33–56 years, recruited in the North-West Province, South Africa. Ambulatory BP and fasting saliva and blood samples were collected. B-mode ultrasound images were obtained to determine CIMT. Results Despite higher usage of anti-hypertensive medication usage ( p = 0.039), a large number of the African men were nocturnal hypertensives (75, 61%). The nocturnal systolic blood pressure (SBP) ( p < 0.001), diastolic blood pressure (DBP) ( p < 0.001) and heart rate ( p < 0.001) of the African men were higher. After stratifying groups into only nocturnal hypertensives the trend was the same (SBP p < 0.001; DBP p < 0.001; heart rate p = 0.058). In the African and Caucasian men, CIMT was linearly predicted by SBP ( β = 0.33, p < 0.001) and DBP ( β = 0.24, p = 0.016) respectively, but not MHPG. Conclusion No associations were firstly demonstrated between MHPG as sympathetic activity marker and CIMT or secondly, between MHPG and nocturnal blood pressure. Novel findings of elevated nocturnal BP evidently seem to promote structural vascular disease in urban African and Caucasian men.
Background High sensitivity cardiac troponin T (hs-cTnT) is a validated marker of myocardial damage and may reflect the degree of silent myocardial ischaemia (SMI) and ventricular strain. Our aim was ...to compare hs-cTnT levels in black and white South Africans taking SMI into consideration. We further explored the capability of hs-cTnT to predict the presence of compensatory systolic hypertension in this South African cohort. Methods A bi-ethnic sex cohort ( n = 404) with similar socioeconomic status (198 black participants and 206 white participants, aged 20-65 years) participated in this target population study where 24 h ambulatory blood pressure, electrocardiogram and overnight fasting cardiometabolic variables were measured. Results Hypertension, higher glycated haemoglobin levels and more frequent and longer SMI events were observed more often in the black participants. Multivariate linear regression analysis showed positive associations between SMI events Adj. R
= 0.19; β 0.35 (0.08-0.62); p < 0.01, SMI event maximum duration Adj. R
= 0.17, β 0.43 (0.16-0.70), p < 0.01, SMI total duration Adj. R
= 0.12; β 0.37 (0.10; 0.65), p = 0.05 and hs-cTnT in black males only. A lower hs-cTnT cut-point ≥4.2 pg/ml for 24 h systolic hypertension was predicted in the black participants compared with ≥5.6 pg/ml in the white participants (area under the curve 0.66-67 (95% CI: 0.57-0.75), p < 0.001) with a respective sensitivity/specificity of 64/68% and 61/71%. Conclusions hs-cTnT may be a potential marker of SMI in the prediction of systolic blood pressure increases, as well as clusters of risk factors for cardiovascular disease. Ethnic- and possibly sex-specific references values for hs-cTnT should be considered for risk stratification.
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